Dilatation catheter balloon made from PEN based homopolymer or random copolymer

ABSTRACT

A balloon for a medical device has a structural layer of a highly crystallized PEN polymer material. The PEN polymer material a polyethylene naphthalate homopolymer or a crystallizable copolyester made up of residues of ethylene glycol, naphthalene dicarboxylic acid (NDC) and at least one member of the group (PA) consisting of terephthalic acid and isophthalic acid. The NDC groups make up about 5% or more of the sum of NDC and PA groups in the copolymer. The balloon is characterized by an ability to withstand a hoop stress of at least 35,000 psi without bursting.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. application Ser. No.08/927,662, filed Sep. 10, 1997, now U.S. Pat. No. 6,358,227, issuedMar. 19, 2002, incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

The present PEN homopolymer and copolymer invention generally relates toa dilation catheter with an inflatable balloon which expands against theinternal walls of a vessel to open or dilate a constriction, stenosis orocclusion of the vessel and, percutaneous transluminal angioplasty(PTA).

The PTA procedure places unique demands on the types of materials neededto fabricate a catheter fitted with an expandable balloon. The physicalproperties and characteristics of a desirable balloon may result incertain characteristics being balanced against others. For instance,very strong thermoplastic materials that are sufficiently strong enoughto allow for minimum balloon wall thicknesses tend to be rigid, hard orstiff compared to more elastomeric materials that tend to be flexible,soft and deformable. Using stronger materials may give a minimum profileballoon but the stiffness of the material may be more likely to injureor traumatize the vascular system as the balloon is positioned to andthen across a stenosis or occlusion.

In the art of catheter balloon manufacture, a variety of thermoplasticpolymers have been used to prepare balloon structures. Polyethyleneterephthalate (PET) of varying intrinsic viscosities have been widelycommercialized.

In the past, PTA catheter balloons have been made from polymericmaterials which gave balloons that may be broadly categorized into twogroups: a) non-compliant balloons and b) compliant balloons.

Non-compliant balloons typically unfold to a nominal diameter and thenstretch or expand only slightly beyond that diameter as the pressure isincreased. See Levy, U.S. Pat. No. Re 32,983, Wang U.S. Pat. No.5,195,969 and Wang U.S. Pat. No. 5,330,428. All three patents describebiaxially oriented polyethylene terephthalate (PET) balloons. Incomparison compliant balloons typically inflate to a nominal diameterand then continue to stretch or expand as the inflation pressure isincreased until the strength of the balloon material is exceeded and theballoon bursts. See Becker U.S. Pat. No. 4,154,244 and Wang, et al, U.S.Pat. No. 5,556,383.

In U.S. Pat. No. 5,270,086 it is proposed that a multilayer ballooncould be made with an outer layer of a high tensile strength polymer andan inner bonding layer of a highly distensible polymer which had goodmelt bond and glue adhesion properties. Among the various materialsproposed for the outer layer is polyethylene naphthalate. Thisreference, however, only exemplifies balloons in which the tensile layeris PET.

It has also been suggested that catheter balloons could be made ofpolyester/polyether block copolymers in which the polyester blocks werepolyesters of naphthalene dicarboxylic acid (U.S. Pat. No. 5,556,383).To date, however, it has not been suggested that balloons made frompolyethylene naphthalate could be formed in a manner to give propertiessignificantly different from those of prior art balloons and it has notbeen demonstrated that such balloons could have substantially improvedproperties relative to commercial materials such as PET.

SUMMARY OF THE INVENTION

It has now been discovered that medical device balloons whose averagestrength is substantially higher than commercially standard PET balloonscan readily be prepared from certain polyethylene naphthalate (PEN)homopolymers or copolymers. The high average strength of the PENballoons is obtained even without exclusion of balloons having cosmeticdefects, such as fish eyes or mottled surfaces.

The inventive catheter balloons have a structural layer of a polymermaterial of PEN homopolymer, or of a PEN copolymer which is acrystallizable copolyester made up of residues of ethylene glycol, ofnaphthalene dicarboxylic acid (NDC), and of a second dicarboxylic acid(PA) which is terephthalic acid or isophthalic acid, or a mixturethereof. The balloons are characterized by an ability to withstand ahoop stress of at least 35,000 psi without bursting, and can readily bedesigned to have a hoop stress of at least 50,000, even for largerdiameter balloons having nominal diameters in the range of 6-30 mm.

The balloons of the invention may be either single layer balloons, ormultilayer balloons. In one preferred embodiment the balloon comprisesan inner layer of PEN homopolymer or copolymer and an outer layer of apolybutylene naphthalate polymer or copolymer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective fragmentary view of a balloon catheter having aballoon thereon made in accordance with the invention.

FIG. 2 is a side sectional view of a balloon in accordance with oneembodiment of the invention.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Referring to FIG. 1 there is shown a catheter 10 comprising an elongatedtube 12 with a balloon 14, made of a layer of PEN polymer in accordancewith the invention hereof, mounted at the distal end thereof.

The PEN homopolymer used in the inventive balloons is a polyester,typically made by transesterification of dimethyl naphthalate andethylene glycol. The PEN copolymers used in the inventive balloons arerandom polyester copolymers. In the copolymers the naphthalate groups(NDC) represent at least 5% of the diacid residues with theterephthalate and/or isophthalate units (PA) representing the balance.The PEN polymers are also highly crystallizable. As a practical matter,this latter feature limits the NDC/PA ratio to be either in the range offrom about 5:95 to about 20:80 or in the range of from about 80:20 to100:0. Preferably the NDC/PA ratio is in the range of from about 80:20to 100:0. More preferably the minimum naphthalate content is about 90%of the diacid residue units, and even more preferably at least 95% ofthe diacid residues are naphthalate groups. The PEN homopolymers and PENrandom copolymers preferably have an intrinsic viscosity less than 0.8dl/g, measured under currently standard conditions for PET.

The PEN homopolymers and PEN copolymers used to make a catheter balloonof the present invention are prepared according to known procedures fromethylene glycol and naphthalene dicarboxylic acid or dimethylnaphthalenedicarboxylate, alone to produce homopolymer, or with dimethylterephthalate and/or dimethyl isophthalate to produce copolymer. Thenaphthalene dicarboxylic acid monomer can be supplied by Amoco whilesome of the homopolymers and copolymers may be commercially availableand are sold under the tradename Vituf® SLX by Shell Chemical, PENHomopolymer 14991 by Eastman Chemical and various PEN homopolymer andcopolymers sold by Teijin Ltd. of Tokyo, Japan under the designationsTN8070; TN8060; TN8756T; and TN8880N and by Hoechst Trevira GmbH & Co.KG, under the trademark Polyclear, including Polyclear N10, PolyclearN90 and Polyclear N100.

The balloons of the invention are particularly suited for use ondilatation catheters used for percutaneous transluminal angioplasty andother minimally invasive procedures. The balloon diameter maybe fromabout 1.5 to about 30 mm, depending on the application to which it isput. The balloons are substantially non-compliant, typically providing aradial expansion of less than 3% when inflation pressure is increasedfrom about 4 atm to about 10 atm, even for relatively large balloons of6-30 mm. The balloons of the invention are engineered to provide amaximum hoop stress at burst, of about 35,000 psi or more, suitablyabove 50,000, and typically in the range of 55,000-65,000 psi.

The PEN homopolymers and PEN/PET copolymer catheter balloons of thisinvention are suitably formed to provide a double wall thickness,measured on the uninflated collapsed balloon, of about 0.0002″-0.0020″.

In one preferred embodiment of the invention, balloon formation is begunby extruding a tube from a melt of the polymer material. Some initialorientation of the PEN homopolymers and PEN/PET copolymers isaccomplished as the material is drawn down during the extrusion process.This process is typically known as machine orientation and is in thedirection of the extrusion operation. It is desirable that the machineorientation be controlled to minimize orientation during extrusion.

Following extrusion, the extruded tube is desirably conditioned at20-30° C. at a controlled humidity in the range of 10-25% for a periodof at least 24 hours. This conditioning provides a constant low moisturelevel in the tube which prevents hydrolysis and helps to optimize theorientation of the polymer in the subsequent blowing steps.

Principle orientation in the machine and transverse directions may beachieved by heating the tubing to temperatures of 135°-165° C. andphysically stretching the extruded homopolymer or random copolymer tubein the axial and radial direction during balloon formation using a freeblowing technique. In this step a pressurized gas is applied to theinside of the tubing. The tubing is expanded freely to a specifieddiameter between cone forms which define the balloon length and conewall configuration. A similar blowing step is described in U.S. Pat. No.4,963,313. The blowing pressure and stretching ratio in the machine andtransverse directions have a controlling effect on final balloon wallthickness. The axial stretch ratio in this step is suitably from about2× to about 5×. The radial stretch is suitably from about 3× to about12×. The tubing diameter to which the balloon is blown in this step isselected so that, after quenching, the inflated but unstressed balloonwill have a diameter in the range of about 50-95% of the final diameterdesired for the balloon. Suitable inflation pressure for this step arein the range of about 100-180 psi, depending on balloon size. Once theballoon reaches the specified diameter it is quenched to roomtemperature and depressurized.

The balloon may be finished in a second, mold blow/crystallization,step. In this step the partially formed balloon of the previous step isplaced in a mold sized to the final diameter and shape desired for theballoon. The mold is closed and the balloon pressurized to preventshrinkage, suitably at a pressure of about 5-50 psi. The mold is heatedto bring the balloon material to a temperature of about 10-60° C. abovethe Tg of the balloon material, with pressurization of the balloonsufficient to expand it to the final desired diameter (typically 170-250psi). This temperature and pressure is held for a brief time, suitablyabout 5-60 seconds, after which the mold is rapidly quenched to ambienttemperature and the balloon removed from the mold.

The final balloons may have a number of visible cosmetic defects, suchas fish eyes or mottled surfaces. Surprisingly such defects do notappear to reduce balloon strength, indicating a remarkable toughness inthe finished balloon.

In another embodiment the balloon is a plural layer laminate including alayer of the PEN polymer as described herein and an outer layer of asofter more elastomeric polymer to provide improved puncture resistanceand to provide a softer less scratchy surface texture to reduce vesseltrauma in use. Various techniques are known for producing suchmultilayer structures, including coextrusion as described in U.S. Pat.No. 5,195,969 (J. Wang, et al.), U.S. Pat. No. 5,290,306 (Trotta et al)and U.S. Pat. No. 5,270,086 (Hamlin), and tube-in-tube techniques asdescribed in copending U.S. application Ser. No. 08/611,664, filed Mar.6, 1996, U.S. Pat. No. 5,512,051 (J. Wang, et al) and in WO 96/04951(Schneider Inc.). The higher extrusion, blowing and crystallizationtemperatures required for the PEN polymers used in the invention,however, can make identification of satisfactory outer layer polymersdifficult. This is particularly so for coextrusions since thetemperature at which the extruder must be heated to melt and extrude thePEN polymer melt temperature can exceed the temperature at which manysofter compliant thermoplastic polymers begin to thermally degrade. Aparticularly preferred multilayer laminate structure of the invention isformed from a coextruded tube having an inner layer of a PEN polymer asdescribed above and an outer layer of a polybutylenenaphthalate/phthalate copolyester. Such copolyesters have good thermalstability and process well at the melt and the subsequent processingtemperatures employed for the PEN polymer. An example of a suitablepolybutylene naphthalate/phthalate copolyester is Nouvelan®, sold byTeijin, Ltd., Japan, a naphthalate/terephthalate copolyester.

Referring to FIG. 2 there is shown a catheter balloon 20 comprising aninner layer 22 of a PEN homopolymer or copolymer as described herein,and an outer layer 24 of a polybutylene naphthalate/phthalatecopolyester.

Those skilled in the art will recognize that other techniques known forpreparing medical device balloons of other thermoplastic polymermaterials can be readily modified in accordance with the teachings andobservations provided herein, and without undue experimentation, toproduce balloons according to the present invention.

In addition to structural polymer layers, the balloon may be providedwith a nonstructural coating layer, for instance a coating of alubricious polymer or of a antithrombotic material, to improve surfaceproperties of the balloon.

The invention is illustrated by the following non-limiting examples.

EXAMPLE 1

Tubing of dimension 0.0257 inch ID and 0.056 inch OD was extruded fromTeijin TN8880N, a linear polyester copolymer ethylene glycol, the diacidresidue of which contains 8% naphthalate and 92% terephthalate units.The tubing was subjected to a two step balloon formation process(free-blow followed by mold-blow/crystallization), as described above,using inflation pressure and times selected to provide a totalcircumferential growth factor of about 9.1 and an axial growth factor ofabout 3.8 to yield final balloons of 6 mm diameter with a single wallthickness of 0.0007 inch. Many balloons displayed some fisheye ormottled surface defects. No balloons were excluded for cosmetic defect.The balloons so prepared had an average hoop stress at burst ofapproximately 55,700 psi.

EXAMPLE 2

Tubing of dimension 0.022 inch ID and 0.054 inch OD was extruded from acommercial PEN homopolymer having an intrinsic viscosity of 0.7. Thetubing was formed into 5 mm balloons in a manner similar to Example 1using a circumferential growth factor of about 8.8 and an axial growthfactor of about 3.7. The final balloons had an average single wallthickness of 0.0009 inch. Many balloons displayed some fisheye ormottled surface defects. No balloons were excluded for cosmetic defect.The balloons so prepared had an average hoop stress at burst ofapproximately 56,100 psi.

EXAMPLE 3

Tubing of dimension 0.028 ID and 0.056 OD was extruded from TeijinTN8880N. The tubing was subjected to a two step balloon formationprocess (free-blow followed by mold-blow/crystallization), as describedabove, to yield final balloons of 6 mm diameter with a double wallthickness of 0.0011-0.0013 inches.

In the second step (mold-blow/crystallization), groups of 15 balloonseach were made using mold temperatures increasing at 5° C. incrementsfrom 140° C. to 175° C. Many balloons displayed some fisheye or mottledsurface defects. No balloons were excluded for cosmetic defect.

At least 14 balloons were burst tested from each group. Balloons mountedon test catheter shafts were inflated at 1 atm intervals until burst.Compliance over the range 74-147 psi inflation pressure was determinedfrom diameter measurements taken at successive pressure intervals.Average hoop stresses at burst for the various balloon groups rangedfrom 56,000-60,000 psi. Average compliance for the various balloongroups ranged between 1.4 and 2.0%.

With only one possible exception, it did not appear that balloons havingcosmetic defects failed at a significantly lower pressure than others inits group.

What is claimed is:
 1. A medical catheter having thereon a balloon, theballoon comprising a structural layer of a PEN polymer material, the PENpolymer material being a) a polyethylene naphthalate homopolymer or b) acrystallizable copolyester comprising residues of i) ethylene glycol,ii) naphthalene dicarboxylic acid and iii) at least one PA residue, saidPA residue being a member of the group consisting of residues ofterephthalic acid and isophthalic acid, the naphthalene dicarboxylicacid residues comprising about 5% or more of the sum of naphthalenedicarboxylic acid residues and PA residues in the copolyester, and, theballoon characterized by an ability to withstand a hoop stress of atleast 50,000 psi without bursting.
 2. A catheter as in claim 1 whereinthe balloon has a double wall thickness of from 0.0002″ to about 0.002″.3. A catheter as in claim 1 wherein the PEN polymer material is saidpolyethylene naphthalate homopolymer.
 4. A catheter as in claim 1wherein the balloon has a radial expansion of about 3% or less wheninflation pressure is increased from 4 atm to burst.
 5. A catheter as inclaim 1 wherein the balloon has a diameter of about 6 mm or more and anaverage burst pressure of about 17 atm or more.
 6. A catheter as inclaim 1 wherein the balloon comprises at least two structural layers,one being said PEN polymer layer and one being a layer of a secondthermoplastic polymer material.
 7. A catheter as in claim 6 wherein theballoon has inner and outer sides and the second thermoplastic polymermaterial is a coextruded layer on the outer side thereof.
 8. A catheteras in claim 1 wherein the balloon has a single structural polymer layer.9. A catheter as in claim 1 wherein said hoop stress is within the rangeof 55,000 to 65,000 psi.
 10. A medical catheter having thereon a ballooncomprising a structural layer of a crystallizable copolyester comprisingresidues of i) ethylene glycol, ii) naphthalene dicarboxylic acid andiii) at least one PA residue, said PA residue being a member of thegroup consisting of residues of terephthalic acid and isophthalic acid,the naphthalene dicarboxylic acid residues constituting at least 80% ofthe sum of naphthalene dicarboxylic acid residues and PA residues.
 11. Acatheter as in claim 10 wherein said naphthalene dicarboxylic acidresidues constitute at least 95% of said sum of naphthalene dicarboxylicacid residues and PA residues.
 12. A catheter as in claim 10 whereinsaid PA residues are terephthalic acid residues.
 13. A catheter as inclaim 10 wherein the balloon has a single structural polymer layer. 14.A catheter as in claim 13 wherein said PA residues are terephthalic acidresidues.
 15. A catheter as in claim 13 wherein the balloon has a singlestructural polymer layer.
 16. A catheter as in claim 13 wherein theballoon further comprises a layer of a second polymer, said secondpolymer being a polybutylene naphthalate homopolymer or a butylenenaphthalate copolymer.
 17. A medical catheter having a balloon thereon,the balloon comprising at least two structural layers, one layer being aPEN polymer layer, the PEN polymer material being a) a polyethylenenaphthalate homopolymer or b) a crystallizable copolyester comprisingresidues of i) ethylene glycol, ii) naphthalene dicarboxylic acid andiii) at least one PA residue, said PA residue being a member of thegroup consisting of residues of terephthalic acid and isophthalic acid,the naphthalene dicarboxylic acid residues at least 80% of the sum ofnaphthalene dicarboxylic acid residues and PA residues in thecopolyester, and one layer being a polybutylene naphthalate homopolymeror a butylene naphthalate copolymer.